Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.
Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.
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DOI：
10.3389/fimmu.2018.01832
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发表时间：
2018
影响因子：
7.3
通讯作者：
Johnson RW
中科院分区：
文献类型：
--
作者：
Matt SM;Allen JM;Lawson MA;Mailing LJ;Woods JA;Johnson RW
衰老导致慢性全身性炎症，可以改变大脑的神经炎症。具体而言，小胶质细胞转变为促炎表型，使其在受到外周免疫信号刺激时易于过度活化。有人提出，某些营养素可以通过防止或逆转小胶质细胞过度活化来延缓大脑衰老。丁酸盐是一种短链脂肪酸（SCFA），主要由结肠中纤维的细菌发酵产生，已被广泛研究，作为组蛋白脱乙酰酶抑制剂，并作为一种有吸引力的治疗候选物，因为丁酸盐也已被证明是抗炎和改善动物模型中的记忆。在这项研究中，我们证明丁酸盐可以减弱老年小鼠小胶质细胞中促炎细胞因子的表达。然而，由于可溶性纤维含量高的饮食导致肠道中丁酸盐产生细菌的增加是否会影响衰老过程中小胶质细胞的活化，这一点仍然没有完全了解。成年和老年小鼠喂食1%纤维素（低纤维）或5%菊粉（高纤维）饮食4周。研究结果表明，饲喂菊粉的小鼠肠道微生物组发生改变，丁酸盐、乙酸盐和总SCFA产量增加。此外，远端结肠的组织学评分表明，低纤维饮食的老年动物具有增加的炎性浸润，这在食用高纤维饮食的动物中显著减少。此外，炎症标志物、表观遗传调节因子和小胶质细胞感觉器（即，感觉体）被饮食和年龄改变，老年动物在高纤维饮食中表现出更抗炎的小胶质细胞特征。总之，在衰老过程中补充高纤维是一种增加丁酸水平的非侵入性策略，这些数据表明，通过添加可溶性纤维（如菊粉）增加丁酸可以平衡与年龄相关的微生物群生态失调，可能导致神经系统的益处。
Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.
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影响因子：
2.1
作者：
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通讯作者：
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